The human protein CD36 is a major endothelial receptor for Plasmodium falciparum parasitized erythrocytes. Several polymorphisms causing CD36 deficiency have been identified to date: T1264G in Kenyan and Gambian patients, and C478T, 539delAC, and 1159insA in Japanese patients. The T1264G polymorphism is reportedly associated with protection from severe malaria in Kenyans, although there is a contradictory report suggesting the susceptibility of T1264G to severe malaria. The polymorphism of CD36 has not been thoroughly studied in Asian malaria patients. In this study, nucleotide sequence variations in exons 4, 5, 6, and 10 of CD36 were investigated in mild and cerebral malaria patients living in northwest Thailand. A novel synonymous substitution T1168C was detected in exon 10, whereas no variation was found in exons 4 and 6. The 539delAC allele in exon 5 was detected in Thai malaria patients, while T1264G, C478T, and 1159insA were not found. The 539delAC allele was observed in three cerebral malaria patients (3/107), but not in mild malaria patients (0/203). The frequency of 539delAC was significantly higher in cerebral malaria patients than in mild malaria patients (p = 0.040, Fisher's exact test). Although independent studies should be performed in order to confirm our findings, the 539delAC allele might be a high-risk variant for cerebral malaria in Thai.